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BACKGROUND: Atherosclerosis is closely linked with glucose metabolism. We aimed to investigate the role of the atherogenic index of plasma (AIP) in the reversal of prediabetes to normal blood glucose levels or its progression to diabetes. METHODS: This multi-center retrospective cohort study included 15,421 prediabetic participants from 32 regions across 11 cities in China, under the aegis of the Rich Healthcare Group's affiliated medical examination institutions. Throughout the follow-up period, we monitored changes in the glycemic status of these participants, including reversal to normal fasting glucose (NFG), persistence in the prediabetic state, or progression to diabetes. Segmented regression, stratified analysis, and restricted cubic spline (RCS) were performed based on the multivariable Cox regression model to evaluate the association between AIP and the reversal of prediabetes to NFG or progression to diabetes. RESULTS: During a median follow-up period of 2.9 years, we recorded 6,481 individuals (42.03%) reverting from prediabetes to NFG, and 2,424 individuals (15.72%) progressing to diabetes. After adjusting for confounders, AIP showed a positive correlation with the progression from prediabetes to diabetes [(Hazard ratio (HR) 1.42, 95% confidence interval (CI):1.24-1.64)] and a negative correlation with the reversion from prediabetes to NFG (HR 0.89, 95%CI:0.81-0.98); further RCS demonstrated a nonlinear relationship between AIP and the reversion from prediabetes to NFG/progression to diabetes, identifying a turning point of 0.04 for reversion to NFG and 0.17 for progression to diabetes. In addition, we observed significant differences in the association between AIP and reversion from prediabetes to NFG/progression to diabetes across age subgroups, specifically indicating that the risk associated with AIP for progression from prediabetes to diabetes was relatively higher in younger populations; likewise, a younger age within the adult group favored the reversion from prediabetes to NFG in relation to AIP. CONCLUSION: Our study, for the first time, reveals a negative correlation between AIP and the reversion from prediabetes to normoglycemia and validates the crucial role of AIP in the risk assessment of prediabetes progression. Based on threshold analysis, therapeutically, keeping the AIP below 0.04 was of paramount importance for individuals with prediabetes aiming for reversion to NFG; preventatively, maintaining AIP below 0.17 was vital to reduce the risk of diabetes onset for those with prediabetes.
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Aterosclerose , Diabetes Mellitus , Estado Pré-Diabético , Adulto , Humanos , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Estudos Retrospectivos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Jejum , Aterosclerose/diagnóstico , Aterosclerose/epidemiologiaRESUMO
BACKGROUND: The impact of dynamic changes in the degree of atherosclerosis on the development of prediabetes remains unclear. This study aims to investigate the association between cumulative atherogenic index of plasma (CumAIP) exposure during follow-up and the development of prediabetes in middle-aged and elderly individuals. METHODS: A total of 2,939 prediabetic participants from the first wave of the China Health and Retirement Longitudinal Study (CHARLS) were included. The outcomes for these patients, including progression to diabetes and regression to normal fasting glucose (NFG), were determined using data from the third wave. CumAIP was calculated as the ratio of the average AIP values measured during the first and third waves to the total exposure duration. The association between CumAIP and the development of prediabetes was analyzed using multivariable Cox regression and restricted cubic spline (RCS) regression. RESULTS: During a median follow-up period of 3 years, 15.21% of prediabetic patients progressed to diabetes, and 22.12% regressed to NFG. Among the groups categorized by CumAIP quartiles, the proportion of prediabetes progressing to diabetes gradually increased (Q1: 10.61%, Q2: 13.62%, Q3: 15.65%, Q4: 20.95%), while the proportion regressing to NFG gradually decreased (Q1: 23.54%, Q2: 23.71%, Q3: 22.18%, Q4: 19.05%). Multivariable-adjusted Cox regression showed a significant positive linear correlation between high CumAIP exposure and prediabetes progression, and a significant negative linear correlation with prediabetes regression. Furthermore, in a stratified analysis, it was found that compared to married individuals, those who were unmarried (including separated, divorced, widowed, or never married) had a relatively higher risk of CumAIP-related diabetes. CONCLUSION: CumAIP is closely associated with the development of prediabetes. High CumAIP exposure not only increases the risk of prediabetes progression but also hinders its regression within a certain range. These findings suggest that monitoring and maintaining appropriate AIP levels may help prevent the deterioration of blood glucose levels.
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Aterosclerose , Biomarcadores , Glicemia , Progressão da Doença , Estado Pré-Diabético , Humanos , Estado Pré-Diabético/sangue , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , China/epidemiologia , Idoso , Fatores de Risco , Glicemia/metabolismo , Medição de Risco , Biomarcadores/sangue , Fatores de Tempo , Estudos Longitudinais , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/diagnóstico , Fatores Etários , PrognósticoRESUMO
BACKGROUND: Venlafaxine (VEN) is a commonly utilized medication for alleviating depression and anxiety disorders. The presence of genetic polymorphisms gives rise to considerable variations in plasma concentrations across different phenotypes. This divergence in phenotypic responses leads to notable differences in both the efficacy and tolerance of the drug. PURPOSE: A physiologically based pharmacokinetic (PBPK) model for VEN and its metabolite O-desmethylvenlafaxine (ODV) to predict the impact of CYP2D6 and CYP2C19 gene polymorphisms on VEN pharmacokinetics (PK). METHODS: The parent-metabolite PBPK models for VEN and ODV were developed using PK-Sim® and MoBi®. Leveraging prior research, derived and implemented CYP2D6 and CYP2C19 activity score (AS)-dependent metabolism to simulate exposure in the drug-gene interactions (DGIs) scenarios. The model's performance was evaluated by comparing predicted and observed values of plasma concentration-time (PCT) curves and PK parameters values. RESULTS: In the base models, 91.1%, 94.8%, and 94.6% of the predicted plasma concentrations for VEN, ODV, and VEN + ODV, respectively, fell within a twofold error range of the corresponding observed concentrations. For DGI scenarios, these values were 81.4% and 85% for VEN and ODV, respectively. Comparing CYP2D6 AS = 2 (normal metabolizers, NM) populations to AS = 0 (poor metabolizers, PM), 0.25, 0.5, 0.75, 1.0 (intermediate metabolizers, IM), 1.25, 1.5 (NM), and 3.0 (ultrarapid metabolizers, UM) populations in CYP2C19 AS = 2.0 group, the predicted DGI AUC0-96 h ratios for VEN were 3.65, 3.09, 2.60, 2.18, 1.84, 1.56, 1.34, 0.61, and for ODV, they were 0.17, 0.35, 0.51, 0.64, 0.75, 0.83, 0.90, 1.11, and the results were similar in other CYP2C19 groups. It should be noted that PK differences in CYP2C19 phenotypes were not similar across different CYP2D6 groups. CONCLUSIONS: In clinical practice, the impact of genotyping on the in vivo disposition process of VEN should be considered to ensure the safety and efficacy of treatment.
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Citocromo P-450 CYP2D6 , Polimorfismo Genético , Cloridrato de Venlafaxina , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2C19/genética , Genótipo , Succinato de DesvenlafaxinaRESUMO
BACKGROUND: Cerebral palsy is a severe motor disability in childhood that poses challenges for children, families, and society. Rhesus macaques are the preferred animals for cerebral palsy model, but surgical excision of motor cortex has low success rate and high cost. In this work, we created cerebral palsy rhesus macaque models by intrathecal injection of bilirubin. METHODS: The puncture point for injection was identified as the intervertebral disc space two, located below the intersection of the iliac crest line and the posterior median line. RESULTS: The models showed abnormal posture and increased muscle tension. Diffuse deposits of bilirubin were found in the basal ganglia from the magnetic resonance imaging. Pathological slides also revealed the presence of brain lesions, such as vacuole formation, contraction of neuronal nuclei, and deep staining of nuclei in the histopathological sections of the hippocampus and basal ganglia. CONCLUSION: The model's symptoms closely resemble those observed in humans with spastic cerebral palsy.
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Paralisia Cerebral , Pessoas com Deficiência , Transtornos Motores , Humanos , Animais , Paralisia Cerebral/veterinária , Paralisia Cerebral/patologia , Macaca mulatta , Análise Custo-BenefícioRESUMO
BACKGROUND: Prediabetes is a high-risk state for diabetes, and numerous studies have shown that the body mass index (BMI) and triglyceride-glucose (TyG) index play significant roles in risk prediction for blood glucose metabolism. This study aims to evaluate the relative importance of BMI combination with TyG index (TyG-BMI) in predicting the recovery from prediabetic status to normal blood glucose levels. METHODS: A total of 25,397 prediabetic subjects recruited from 32 regions across China. Normal fasting glucose (NFG), prediabetes, and diabetes were defined referring to the American Diabetes Association (ADA) criteria. After normalizing the independent variables, the impact of TyG-BMI on the recovery or progression of prediabetes was analyzed through the Cox regression models. Receiver Operating Characteristic (ROC) curve analysis was utilized to visualize and compare the predictive value of TyG-BMI and its constituent components in prediabetes recovery/progression. RESULTS: During the average observation period of 2.96 years, 10,305 individuals (40.58%) remained in the prediabetic state, 11,278 individuals (44.41%) recovered to NFG, and 3,814 individuals (15.02%) progressed to diabetes. The results of multivariate Cox regression analysis demonstrated that TyG-BMI was negatively associated with recovery from prediabetes to NFG and positively associated with progression from prediabetes to diabetes. Further ROC analysis revealed that TyG-BMI had higher impact and predictive value in predicting prediabetes recovering to NFG or progressing to diabetes in comparison to the TyG index and BMI. Specifically, the TyG-BMI threshold for predicting prediabetes recovery was 214.68, while the threshold for predicting prediabetes progression was 220.27. Additionally, there were significant differences in the relationship of TyG-BMI with prediabetes recovering to NFG or progressing to diabetes within age subgroups. In summary, TyG-BMI is more suitable for assessing prediabetes recovery or progression in younger populations (< 45 years old). CONCLUSIONS: This study, for the first time, has revealed the significant impact and predictive value of the TyG index in combination with BMI on the recovery from prediabetic status to normal blood glucose levels. From the perspective of prediabetes intervention, maintaining TyG-BMI within the threshold of 214.68 holds crucial significance.
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Diabetes Mellitus , Estado Pré-Diabético , Humanos , Pessoa de Meia-Idade , Glucose/metabolismo , Índice de Massa Corporal , Glicemia/metabolismo , Triglicerídeos , Diabetes Mellitus/diagnóstico , Estudos de Coortes , Jejum , Fatores de RiscoRESUMO
BACKGROUND: α-fetoprotein (AFP) response has been demonstrated as a biomarker for unresectable hepatocellular carcinoma (uHCC) patients receiving immunotherapy, but its definition is still unclear. This exploratory study investigated the AFP trajectory and clinical outcomes of receiving atezolizumab plus bevacizumab (Atez/Bev) therapy. METHODS: This secondary analysis used the Atez/Bev arm data of phase III IMbrave150 study to distinguish potential AFP changing rate trajectories through latent class trajectory models. The multivariable Cox models were applied to calculate adjusted hazard ratios (HRs) and 95% CIs for clinical outcomes. RESULTS: Three distinct trajectories were identified among the uHCC patients with 7 times (range, 3 to 28) of AFP measurements: low-stable (50.0%, n = 132), sharp-falling (13.3%, n = 35), and high-rising (36.7%, n = 97). Compared with the high-rising class, HRs of disease progression were 0.52 (95% CI: 0.39, 0.70) and 0.26 (95% CI: 0.16, 0.43) for the low-stable class and sharp-falling class, respectively. In contrast, HRs of death were 0.59 (95% CI: 0.40, 0.81) and 0.30 (95% CI: 0.16, 0.57) for the two groups after propensity score adjustment. Besides, AFP trajectories had the highest relative importance of each covariate to survival. DISCUSSION: There are three distinct AFP trajectories in uHCC patients receiving Atez/Bev, and it is an independent biomarker for clinical outcomes.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , alfa-Fetoproteínas , Bevacizumab/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
Second near infrared (NIR-II, 1000-1700 nm) fluorescence lifetime imaging is a powerful tool for biosensing, anti-counterfeiting, and multiplex imaging. However, the low photoluminescence quantum yield (PLQY) of fluorescence probes in NIR-II region limits its data collecting efficiency and accuracy, especially in multiplex molecular imaging in vivo. To solve this problem, lanthanide-doped nanoparticles (NPs) ß-NaErF4 : 2%Ce@NaYbF4 @NaYF4 with high PLQY and tunable PL lifetime through multi-ion doping and core-shell structural design, are presented. The obtained internal PLQY can reach up to 50.1% in cyclohexane and 9.2% in water under excitation at 980 nm. Inspired by the above results, a fast NIR-II fluorescence lifetime imaging of whole-body vascular in mice is successfully performed by using the homebuilt fluorescence lifetime imaging system, which reveals a murine abdominal capillary network with low background. A further demonstration of fluorescence lifetime multiplex imaging is carried out in molecular imaging of atherosclerosis cells and different organs in vivo through NPs conjugating with specific peptides and different injection modalities, respectively. These results demonstrate that the high PLQY NPs combined with the homebuilt fluorescence lifetime imaging system can realize a fast and high signal-to-noise fluorescence lifetime imaging; thus, opening a road for multiplex molecular imaging of atherosclerosis.
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Aterosclerose , Elementos da Série dos Lantanídeos , Nanopartículas , Animais , Camundongos , Elementos da Série dos Lantanídeos/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Imagem Óptica , Nanopartículas/químicaRESUMO
Food wastes can be hydrolyzed into soluble microbial substrates, contributing to sustainability. Halomonas spp.-based Next Generation Industrial Biotechnology (NGIB) allows open, unsterile fermentation, eliminating the need for sterilization to avoid the Maillard reaction that negatively affects cell growth. This is especially important for food waste hydrolysates, which have a high nutrient content but are unstable due to batch, sources, or storage conditions. These make them unsuitable for polyhydroxyalkanoate (PHA) production, which usually requires limitation on either nitrogen, phosphorous, or sulfur. In this study, H. bluephagenesis was constructed by overexpressing the PHA synthesis operon phaCABCn (cloned from Cupriavidus necator) controlled by the essential gene ompW (encoding outer membrane protein W) promoter and the constitutive porin promoter that are continuously expressed at high levels throughout the cell growth process, allowing poly(3-hydroxybutyrate) (PHB) production to proceed in nutrient-rich (also nitrogen-rich) food waste hydrolysates of various sources. The recombinant H. bluephagenesis termed WZY278 generated 22 g L-1 cell dry weight (CDW) containing 80 wt% PHB when cultured in food waste hydrolysates in shake flasks, and it was grown to 70 g L-1 CDW containing 80 wt% PHB in a 7-L bioreactor via fed-batch cultivation. Thus, unsterilizable food waste hydrolysates can become nutrient-rich substrates for PHB production by H. bluephagenesis able to be grown contamination-free under open conditions.
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Halomonas , Poli-Hidroxialcanoatos , Eliminação de Resíduos , Poliésteres/metabolismo , Halomonas/metabolismo , Alimentos , Genes Essenciais , Poli-Hidroxialcanoatos/genética , Poli-Hidroxialcanoatos/metabolismo , Hidroxibutiratos/metabolismoRESUMO
This study aimed to explore the effect of Ganmai Dazao Decoction on the ethology of rats with posttraumatic stress disorder(PTSD) and study the related mechanism through the changes in magnetic resonance imaging and protein expression. Sixty rats were randomly divided into 6 groups, namely the normal group, the model group, the low(1 g·kg~(-1)), medium(2 g·kg~(-1)), and high-dose Ganmai Dazao Decoction groups(4 g·kg~(-1)), and the positive control group(intragastric administration with 10.8 mg·kg~(-1) of fluoxetine), with 10 rats in each group. Two weeks after inducing PTSD by single-prolonged stress(SPS) in rats, the positive control group was given fluoxetine hydrochloride capsule by gavage, the low, medium, and high-dose groups were given Ganmai Dazao Decoction by gavage, and both the normal group and the model group were given the same volume of normal saline by gavage, each for 7 days. The open field experiment, elevated cross elevated maze, forced swimming experiment, and new object recognition test were carried out for the behavioral test. Three rats in each group were selected to detect the expression of neuropeptide receptor Y1(NPY1R) protein in the hippocampus by Western blot. Then, the other three rats in each group were selected to use the 9.4T magnetic resonance imaging experiment to observe the overall structural changes in the brain region and the anisotropy fraction of the hippocampus. The results of the open field experiment showed that the total distance and central distance of rats in the model group were significantly lower than those in the normal group, and the total distance and central distance of rats in the middle and high-dose Ganmai Dazao Decoction groups were higher than those in the model group. The results of the elevated cross maze test showed that medium and high-dose Ganmai Dazao Decoction remarkably increased the number of open arm entries and the residence time of open arm of rats with PTSD. The results of the forced swimming experiment showed that the immobility time in the water of the model group rats was significantly higher than that of the normal group, and Ganmai Dazao Decoction hugely reduced the immobility time in the water of rats with PTSD. The results of the new object recognition test showed that Ganmai Dazao Decoction significantly increased the exploration time of new objects and familiar objects in rats with PTSD. The results of Western blot showed that Ganmai Dazao Decoction significantly reduced the expression of NYP1R protein in the hippocampus of rats with PTSD. The 9.4T magnetic resonance examination found that there was no significant difference in the structural image among the groups. In the functional image, the fractional anisotropy(FA value) of the hippocampus in the model group was significantly lower than that in the normal group. The FA value of the hippocampus in the middle and high-dose Ganmai Dazao Decoction groups was higher than that in the model group. Ganmai Dazao Decoction reduces the injury of hippocampal neurons by inhibiting the expression of NYP1R in the hippocampus of rats with PTSD, thereby improving the nerve function injury of rats with PTSD and playing a neuroprotective role.
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Etologia , Transtornos de Estresse Pós-Traumáticos , Animais , Ratos , Fluoxetina , Hipocampo , Aprendizagem em LabirintoRESUMO
PURPOSE: Quantitative T1 and T2 mapping in non-human primates with whole-brain coverage is challenged by the requirement of sub-millimeter resolution and the inhomogeneity of the transmit magnetic field (B1+ ) covering a large field of view. The goal of the current study is to develop a magnetic resonance fingerprinting (MRF) method for simultaneous T1 and T2 mapping of the entire macaque brain within feasible scan time. METHODS: A three-dimensional (3D) MRF sequence with both inversion- and T2 -preparation modules was developed and evaluated on a 9.4 T preclinical scanner. Data acquisition used a 3D stack-of-spirals trajectory, with undersampling along both the in-plane and the through-plane directions. The effect of B1+ inhomogeneity was accounted for by matching the acquired fingerprint to a dictionary simulated with the B1+ factors measured from a separate scan. In vitro and ex vivo studies were performed to evaluate the accuracy and the undersampling capacity of the MRF method. The application of the MRF method for in vivo, brain-wide T1 and T2 mapping was demonstrated on macaques at 4, 6, and 12 years of age. RESULTS: The MRF method enabled highly repeatable T1 and T2 mapping at high spatial resolution (0.35 × 0.35 × 1 mm3 ) with an acceleration factor of 24. In vivo studies showed significant age-related T2 reduction in deep gray nuclei including the globus pallidus, the putamen, and the caudate nucleus. CONCLUSIONS: This study demonstrates the first MRF study for brain-wide, multi-parametric quantification in non-human primates with sub-millimeter resolution.
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Macaca , Imageamento por Ressonância Magnética , Animais , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Imagens de FantasmasRESUMO
The remobilization of non-structural carbohydrates (NSCs) in the stem is essential for rice grain filling so as to improve grain yield. We conducted a two-year field experiment to deeply investigate their relationship. Two large-panicle rice varieties with similar spikelet size, CJ03 and W1844, were used to conduct two treatments (removing-spikelet group and control group). Compared to CJ03, W1844 had higher 1000-grain weight, especially for the grain growth of inferior spikelets (IS) after removing the spikelet. These results were mainly ascribed to the stronger sink strength of W1844 than that of CJ03 contrasting in the same group. The remobilization efficiency of NSC in the stem decreased significantly after removing the spikelet for both CJ03 and W1844, and the level of sugar signaling in the T6P-SnRK1 pathway was also significantly changed. However, W1844 outperformed CJ03 in terms of the efficiency of carbon reserve remobilization under the same treatments. More precisely, there was a significant difference during the early grain-filling stage in terms of the conversion of sucrose and starch. Interestingly, the sugar signaling of the T6P and SnRK1 pathways also represented an obvious change. Hence, sugar signaling may be promoted by sink strength to remobilize the NSCs of the rice stem during grain filling to further advance crop yield.
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Oryza , Carboidratos , Grão Comestível/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Açúcares/metabolismoRESUMO
BACKGROUND: Autologous platelet concentrate has been widely used to encourage the regeneration of hard and soft tissues. Up to now, there are three generations of autologous platelet concentrates. Many studies have shown that the three autologous concentrates have different effects, but the specific diversities have not been studied. The purpose of this study was to explore and compare the effects of platelet-rich fibrin, concentrated growth factor and platelet-poor plasma on the healing of tooth extraction sockets in New Zealand rabbits. METHODS: A total of 24 healthy male New Zealand white rabbits aged 8-12 weeks were selected. The experimental animals were randomly divided into four groups: three experimental groups were respectively implanted with PPP, CGF and PRF gel after bilateral mandibular anterior teeth were extracted, and the control group did not implant any material. The alveolar bone of the mandibular anterior region was taken at 2, 4 and 8 weeks after operation. The height and width of the extraction wound were detected by CBCT, the growth of the new bone was observed by HE and Masson staining, and the expression of osteogenic genes was detected by real-time PCR. Data were analyzed using IBM SPSS statistical package 22.0. RESULTS: The radiological results showed that alveolar bone resorption in all groups gradually increased over time. However, the experimental groups showed lower amounts of bone resorption. The histological results showed that new bone formation was observed in all groups. Over time, the new bone trabeculae of the CGF group became closely aligned while those in the PPP and PRF groups remained scattered. PCR results showed that the expression of BMP-2 and ALP was higher in the experimental groups than the control group. CONCLUSION: In conclusion, the application of PRF, CGF and PPP in tooth extraction sockets effectively promoted bone regeneration. CGF showed more effective bone induction and tissue regeneration ability in the long term.
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Perda do Osso Alveolar , Fibrina Rica em Plaquetas , Animais , Masculino , Coelhos , Perda do Osso Alveolar/patologia , Peptídeos e Proteínas de Sinalização Intercelular , Extração Dentária/métodos , Alvéolo Dental/cirurgiaRESUMO
AIM: The aim of this study is to investigate the effect of maternal nicotine exposure (MNE) on the development of metabolic associated fatty liver disease (MAFLD) in adulthood offspring and the underlying mechanism. METHODS: Pregnant mice (n = 22) were subcutaneously injected with either saline vehicle (n = 11) or nicotine (n = 11) twice a day on gestational days 11-21. Offspring mice (n = 176) from both groups were weaned at postnatal day 21, and for 6 months after postnatal day 21, 96 mice were fed either a standard chow diet (n = 48) or a high-fat diet (n = 48). Serum lipid indicators, liver function indicators, insulin, and liver mitochondrial respiration were analyzed. The expression levels of fibrosis-related proteins, phosphorylated PI3K, phosphorylated Akt, sterol regulatory element-binding transcription factor 1 (SREBP1c), and peroxisome proliferator-activated receptor alpha (PPAR-α) were detected in the liver by immunohistochemistry and Western blotting. RESULTS: MNE significantly decreased the weight of both maternal and offspring mice (~30%) and inhibited organ growth in offspring mice (P < .05). MNE also significantly increased serum levels of total bile acid, triglycerides, total cholesterol, glucose, alanine aminotransferase, aspartate aminotransferase, low-density lipoprotein, and insulin while decreasing serum high-density lipoprotein levels and mitochondrial respiration activity in mice fed either the normal diet or high-fat diet (all P < .05). These effects of MNE on lipid metabolism and insulin resistance were mediated via PI3K and Akt phosphorylation and down-regulation of SREBP1c and PPAR-α. CONCLUSION: Our data indicate MNE induces lipid metabolism disorder and insulin resistance to promote MAFLD progression in adult offspring through activation of PI3K/Akt signaling and suppression of SREBP1c and PPARα protein expression.
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Fígado Gorduroso , Resistência à Insulina , Efeitos Tardios da Exposição Pré-Natal , Animais , Dieta Hiperlipídica , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/metabolismo , Feminino , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos , Nicotina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Gravidez , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Ynamides, though relatively more stable than ynamines, are still moisture-sensitive and prone to hydration especially under acidic and heating conditions. Here we report an environmentally benign, robust protocol to synthesize sulfonamide-based ynamides and arylynamines via Sonogashira coupling reactions in water, using a readily available quaternary ammonium salt as the surfactant.
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BACKGROUND: Although the relationship between gout and cardiovascular has been well demonstrated, there is little information about the difference between gout with cerebrovascular disease and cardiovascular disease. In this study, the differences between gout with cerebral infarction (gout+CI) and gout with coronary heart disease (gout+CHD) and related factors that affect serum uric acid (sUA) levels in gout+CI were investigated by a cross-sectional study. METHOD: The patients from Jiangxi Provincial People's Hospital with gout+CHD, gout+CI, and gout with coronary heart disease and cerebral infarction (gout+CHD+CI) between 2016 and 2020 were included in this study, and the medical record data were collected and analyzed. RESULTS: We observed significant differences in age, drinking, hypertension, long-term use of diuretics and NSAIDs, sUA, CRE, and blood glucose in patients with gout+CHD and gout+CI. The sUA level was significantly positively correlated with smoking, CRE, and TG in the gout+CI group and was only positively correlated with CRE in the gout+CHD group and the gout+CHD+CI group (p < 0.05). Interestingly, the sUA level was only negatively correlated with the age and gender in the gout+CI group (p < 0.05). After excluding factors with no significant statistical effect, only age, gender, smoking, CRE, and TG were included in the multiple linear regression model. It suggested that smoking, CRE, and TG are positively correlated with the sUA level, while age was negatively correlated with the sUA level. CONCLUSIONS: There are many discrepancies in clinical characteristics between gout+CHD patients and gout+CI patients, especially that the factors that affect UA levels are significantly different. The data also suggested that uric acid-lowering therapy may need to be strengthened in the young gout+CI patients with a history of smoking.
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Gota , Hipertensão , Infarto Cerebral , Estudos Transversais , Humanos , Ácido ÚricoRESUMO
Quantitative studies of art and aesthetics are representative of interdisciplinary research. In this work, we conducted a large-scale quantitative study of 36,000 paintings covering both Eastern and Western paintings. The information entropy and wavelet entropy of the images were calculated based on their complexity and energy. Wavelet energy entropy is a feature that can characterize rich information in images, and this is the first study to introduce this feature into aesthetic analysis of art paintings. This study shows that the process of entropy change coincides with the development process of art painting. Further, the experimental results demonstrate an important change in the evolution of art painting, and since the rise of modern art in the twentieth century, the entropy values in painting have started to become diverse. In comparison with Western paintings, Eastern paintings have distinct low entropy characteristics in which the wavelet entropy feature of the images has better results in the machine learning classification task of Eastern and Western paintings (i.e., the F1 score can reach 97%). Our study can be the basis for future quantitative analysis and comparative research in the context of Western and Eastern art aesthetics.
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Magnetic resonance imaging (MRI) is advantageous in the diagnosis of deep internal cancers, but contrast agents (CAs) are always needed to improve MRI sensitivity. Gadolinium (Gd)-based agents are routinely used as T1-dominated CAs in clinic but using intracellularly formed Gd nanoparticles to enhance the T2-weighted MRI of tumor in vivo at high magnetic field has not been reported. Herein, we rationally designed a "smart" Gd-based probe Glu-Cys(StBu)-Lys(DOTA-Gd)-CBT (1), which was subjected to γ-glutamyltranspeptidase (GGT) cleavage and an intracellular CBT-Cys condensation reaction to form Gd nanoparticles (i.e., 1-NPs) to enhance the T2-weighted MR contrast of tumor in vivo at 9.4 T. Living cell experiments indicated that the 1-treated HeLa cells had an r2 value of 27.8 mM-1 s-1 and an r2/r1 ratio of 10.6. MR imaging of HeLa tumor-bearing mice indicated that the T2 MR contrast of the tumor enhanced 28.6% at 2.5 h post intravenous injection of 1. We anticipate that our probe 1 could be employed for T2-weighted MRI diagnosis of GGT-related cancers in the future when high magnetic field is available in clinic.
Assuntos
Meios de Contraste/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Neoplasias/diagnóstico , gama-Glutamiltransferase/administração & dosagem , Animais , Meios de Contraste/química , Gadolínio/administração & dosagem , Gadolínio/química , Células HeLa , Humanos , Imageamento por Ressonância Magnética/métodos , Nanopartículas Metálicas/química , Camundongos , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , gama-Glutamiltransferase/químicaRESUMO
OBJECTIVES: To investigate the applicability and value of ultrasound (US) in the diagnosis of anorectal atresia. METHODS: Between January 2008 and January 2016, we prospectively evaluated 63,101 fetuses (gestational age, 20-38 weeks), including low- and high-risk populations using 2-dimensional US scans. An abnormal imaging finding was defined as an anal canal diameter of less than the 95% confidence interval (small anal canal) of the normal range or the absence of an anal canal and rectum. Imaging findings were considered normal on detection of an anal canal with a normal width and the absence of abnormalities. Prenatal imaging findings were confirmed by a postnatal or postmortem examination. RESULTS: Among the investigated fetuses, 28 showed evidence of anorectal atresia on US scans, and 22 of those with anorectal atresia had additional anomalies. Six cases of isolated anorectal atresia were successfully detected during the preclusive prenatal US scans. Four cases of a low imperforate anus (including 2 covered anuses) yielded false-negative results, indicating a diagnostic rate of 87.5% (28 of 32). The normal appearance of the fetal rectum and anal canal ruled out anorectal atresia in 30 fetuses with a dilated colon. Additionally, there were 3 false-positive cases, in which a narrow anal canal was observed. CONCLUSIONS: Identifying the abnormal appearance or absence of the fetal anal canal and rectum on preclusive US anomaly scans is useful for prenatal diagnosis or exclusion of anorectal atresia, which may help improve the detection of isolated anorectal atresia. Furthermore, a combined evaluation of the longitudinal and axial appearances of the fetal anal canal and rectum can improve diagnostic accuracy.
Assuntos
Malformações Anorretais/diagnóstico por imagem , Malformações Anorretais/embriologia , Ultrassonografia Pré-Natal/métodos , Canal Anal/diagnóstico por imagem , Canal Anal/embriologia , Feminino , Humanos , Gravidez , Estudos Prospectivos , Reto/diagnóstico por imagem , Reto/embriologia , Reprodutibilidade dos TestesRESUMO
For rat spinal magnetic resonance imaging (MRI) experiments, due to the lower main magnetic field strength, shallower detected depth and poor spatial compatibility of the traditional radio frequency (RF) coil, the image signal-to-noise ratio (SNR) of rat spinal was rather lower. In this paper, a RF coil for rat spinal MRI at 9.4 T was developed to improve the image quality and at the same time to avoid the space limitation while scanning in special conditions (cardiac catheterization, etc.). In this article, open birdcage structure was built and magnetic field distribution was calculated. The phantom and rat spine MRI imaging were experimented at 9.4 T to verify the advantage of the coil in rat spine MRI application.
RESUMO
Quantitative susceptibility mapping (QSM) can provide tissue susceptibility information and has been adapted for clinical research and diagnosis. QSM of monkey brain in vivo at 9.4 T has not been demonstrated so far. In this study 9.4 T in vivo monkey brain QSM was performed with 200 µm isotropic high-resolution. It was found that the inherent singularity problem for QSM diverged significantly at ultra-high image resolution during regularization process and resulted in severe image artifacts. The K-space division (TKD) was applied to eliminate the artifacts, with an optimal threshold level between 0.2 and 0.3. High resolution QSM of monkey brain in vivo can thus provide a novel tool for brain research.